Benzodiazepine Antagonist in the Treatment of Human Hepatic Encephalopathy
Recently it was suggested that hepatic encephalopathy (HE) is mediated by an increased GABA-ergic tone. The logical consequence of such a hypothesis is the use of antagonists of the GABA -benzodiazepine receptor for treatment of HE. The experience with these drugs in human HE is limited. In order to get an estimate of the efficacy of this type of drug in humans 20 consecutive episodes of HE in 17 patients with acute or chronic liver failure were treated with flumazenil. All patients entered into the study were encephalopathic for up to 120 hours and failed to respond to conventional therapy. After an observation period of 8 hours, 15 mg of flumazenil were infused intravenously over 3 hours. Before and after treatment patients were examined neurologically and the Glasgow coma scale was calculated. In addition, somatosensory evoked potentials were recorded. In 5 out of 11 episodes in 10 patients with fulminant hepatic failure and in 7 out of 9 episodes in 7 patients with cirrhosis an unequivocal amelioration of HE was observed. The response to treatment occurred very rapidly. After stopping treatment in 8 out of these 12 episodes HE worsened again after 2 to 4 hours. The favourable clinical response was also documented by improvement of somatosensory evoked potentials. In 5 of the 8 episodes not reacting to flumazenil patients had signs of increased intracranial pressure. These findings indicate that flumazenil may be valuable in treatment of acute HE occurring in fulminant hepatic failure or in decompensated cirrhosis.
Furthermore a patient with portal systemic encephalopathy refractory to standard therapy following extensive liver resection and construction of a portocaval shunt was treated with flumazenil 25 mg twice daily. Before treatment she was encephalopathic with 12 attacks of coma within 2 years. On treatment with flumazenil all signs of HE abated in spite of unrestricted dietary protein intake. After one year treatment with flumazenil was stopped. Two days later she became comamonths. Since reinstitution of flumazenil she is well for 16 months of follow up without any signs of HE. She does not require a protein restricted diet. The favourable response of this patient to treatment with flumazenil suggests that flumazenil may be also valuable in long term management of portal systemic encephalopathy.
KeywordsHepatic Encephalopathy Glasgow Coma Scale Fulminant Hepatic Failure Hepatic Coma Chronic Liver Failure
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